These experiments are designed to determine whether adolescents at risk for substance abuse (SA) exhibit impaired cognitive performance on a task that reveals a deficit in performance by adults with a history of SA. Abnormal cognitive performance in adults after long-term exposure to drugs of abuse can reflect either vulnerability to SA (primary effect) or drug effects on the brain (secondary effect). This study tests the hypothesis that a predisposing cognitive deficit in adolescents contributes to risk for substance abuse. To date, 81 adolescents completed the initial phase of the study and 31 have completed their 3-year follow-up visit. Healthy adolescents (N=31) performed similarly to healthy adults on a Gambling task (GT), which targets impulsivity and judgment and depends on orbitofrontal cortical function. Substance abusing adults tend to perform more poorly than healthy adults on this task. Adolescents at risk for substance abuse (N=33) also perform more poorly on this task than healthy adolescents, suggesting that abnormal performance on this task may precede exposure to substances of abuse. These results are preliminary and await confirmation by studying a larger population, and assessing directly the significance of the findings in follow-up data. Self-reports and parental reports of difficulties associated with executive function (e.g., planning, organization and initiation) are significantly correlated with an external locus of control in 37 adolescent boys (aged 12-18, with and without ADHD) enrolled in this study. An external locus of control, which has been associated with adaptation and emotional difficulties such as depression and anxiety, is also sensitive to the onset of substance abuse. Follow-up studies of these participants will test the association of perceived control with dysfunctional adaptations such as substance abuse.